Metformin, sold under the brand name Glucophage among others, is the first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight.[8] It is also used in the treatment of polycystic ovary syndrome. It is not associated with weight gain and is taken by mouth.

Metformin is generally well tolerated. Common adverse effects include diarrhea, nausea, and abdominal pain.[6] It has a low risk of causing low blood sugar. High blood lactic acid level is a concern if the medication is used in overly large doses or prescribed in persons with severe kidney problems. It is not recommended in those with significant liver disease. Metformin is a biguanide antihyperglycemic agent. It works by decreasing glucose production by the liver, by increasing the insulin sensitivity of body tissues, and by increasing GDF15 secretion, which reduces appetite and caloric intake.

Metformin was discovered in 1922. French physician Jean Sterne began the study in humans in the 1950s. It was introduced as a medication in France in 1957 and the United States in 1995. It is on the World Health Organization's List of Essential Medicines. Metformin is the most widely used medication for diabetes taken by mouth. It is available as a generic medication. In 2018, it was the fourth-most commonly prescribed medication in the United States, with more than 83 million prescriptions.

The United Kingdom Prospective Diabetes Study, a large clinical trial performed in 1980–90s, provided evidence that metformin reduced the rate of adverse cardiovascular outcomes in overweight patients with type 2 diabetes relative to other antihyperglycemic agents. Accumulated evidence from other and more recent trials, though, reduced confidence in the efficacy of metformin for cardiovascular disease prevention. Outcomes are improved even in those with some degree of kidney disease, heart failure, or chronic liver disease.

Treatment guidelines for major professional associations, including the European Association for the Study of Diabetes, the European Society for Cardiology, and the American Diabetes Association, now describe evidence for the cardiovascular benefits of metformin as equivocal.

In 2017, the American College of Physicians's guidelines were updated to recognize metformin as the first-line treatment for type 2 diabetes. These guidelines supersede earlier reviews. For example, a 2014 review found tentative evidence that people treated with sulfonylureas had a higher risk of severe low blood sugar events (RR 5.64), though their risk of nonfatal cardiovascular events was lower than the risk of those treated with metformin (RR 0.67). Not enough data were available at that time to determine the relative risk of death or of death from heart disease.

Metformin use reduces body weight in persons with type 2 diabetes mellitus in contrast to sulfonylureas, which are associated with weight gain. Some evidence shows that metformin is associated with weight loss in obesity in the absence of diabetes. Metformin has a lower risk of hypoglycemia than the sulfonylureas, although hypoglycemia has uncommonly occurred during intense exercise, calorie deficit, or when used with other agents to lower blood glucose. Metformin modestly reduces low density lipoprotein and triglyceride levels.